Genetic factor underlies weight gain after use of antipsychotic drugs

Authors of a research letter in this week's issue of THE LANCET suggest that there is a genetic basis for the weight gain associated with the use of antipsychotic drugs.

Increased body fat is a side-effect of treatment with antipsychotic drugs for schizophrenia; this often leads to further medical problems associated with obesity as well as poor adherence to treatment. A serotonin receptor (5-hydroxytryptamine 2C receptor [5-HT2C]) has been associated with this effect. Gavin Reynolds from the University of Sheffield, UK, and colleagues aimed to establish whether a genetic alteration of the promoter region of this receptor affects weight gain after drug treatment in patients with schizophrenia.

123 Chinese in-patients with first-time schizophrenia took part in the study. They received conventional drug treatment with antipsychotic drugs, were given a standard hospital diet, and underwent blood testing to identify 5-HT2C receptor gene status. After six weeks, 28% of patients with the wildtype (most common) genotype had an increased bodyweight of 7% or more compared with none of the patients with the variant (759T) allele. At ten weeks the corresponding proportions were 51% for the wildtype genotype and 15% for the variant, respectively.

Gavin Reynolds comments: "We have identified a genetic factor that indicates the likelihood of developing a serious side effect of psychiatric drug treatment. If confirmed, these findings could provide the basis for a simple test to determine a patient's liability to develop drug-induced weight gain, and assist the doctor in choosing the most appropriate drug treatment. Such predictive tests are likely to be common in the surgery of the future, where genetic profiling would be used to indicate the most effective and least harmful treatment, individualised for the patient." (quote by e-mail; does not appear in published paper).


Contact: Richard Lane

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